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Item Arterial stiffness and its relationship to clinic and ambulatory blood pressure: a longitudinal study in non-dialysis chronic kidney disease(Oxford, 2017) Agarwal, Rajiv; Medicine, School of MedicineBackground Both arterial stiffness and systolic blood pressure (BP) are established cardiovascular risk factors, yet little is known about their interrelationship in chronic kidney disease (CKD). The goal of this prospective study was to describe the trajectory of aortic pulse wave velocity (PWV) and BP and to compare the longitudinal interrelationship of BP (clinic and 24 h ambulatory recording) with the PWV. Methods Clinic BP was taken in two ways: at the time of the measurement of the PWV (Clinic-S) and as an average of triplicate measurements on three separate occasions within 1 week (Clinic-M). 24 h ambulatory BP was measured using a validated monitor and PWV was measured in the aorta using an echo-Doppler technique. Results Among 255 veterans with CKD followed for over up to 4 years, the rate of change of log PWV was inversely related to the baseline PWV; the trajectories were variable among individuals and the net population change was no different from zero. In contrast, systolic BP significantly increased, but linearly, and a strong relationship was seen between cross-sectional and longitudinal changes in Clinic-M systolic BP and log PWV. In contrast, a longitudinal relationship between Clinic-S and log PWV was absent. In the case of 24-h ambulatory BP, a strong cross-sectional change was seen between awake and 24 h systolic BP but not between sleep BP and log PWV Conclusion In conclusion, among people with CKD, the PWV changes over time and is inversely related to the baseline PWV. An average of clinic BP measurements taken over three visits, but not single measurements, are useful to assess the PWV and its change over time. Differences exist between ambulatory BP monitoring recording during the sleep and awake states in their ability to predict the PWV. Taken together, these data support the view that among those with CKD not on dialysis, targeting clinic BP taken on multiple occasions using a standardized methodology or daytime ambulatory systolic BP may slow the progression of arterial damage.Item Delayed systolic blood pressure recovery following exercise as a mechanism of masked uncontrolled hypertension in chronic kidney disease(Oxford, 2017-10) Agarwal, Rajiv; Pappas, Maria K.; Medicine, School of MedicineBackground Among people treated for hypertension, the presence of elevated blood pressure (BP) out of the clinic but normal BP in the clinic is called masked uncontrolled hypertension (MUCH). What causes MUCH remains unknown. The purpose of this study was to answer the question of whether patients with MUCH have an increased hemodynamic reactivity to exercise and delayed hemodynamic recovery following exercise. Methods Four groups were compared: controlled hypertension (CH, n = 58), MUCH (n = 34) and uncontrolled hypertension (UCH, n = 12), all of which had chronic kidney disease (CKD), and a group of healthy normal volunteers who did not have hypertension or CKD (n = 16). All participants underwent assessment of 24-h ambulatory BP monitoring, BP measurement during a graded symptom-limited exercise using a cycle ergometer and BP recovery over 7 min following exercise. Results Exercise-induced increase in systolic BP was similar among the four groups. When compared with healthy controls, recovery of systolic BP following termination of exercise was blunted among the CKD groups in unadjusted (P < 0.0001) and adjusted (P < 0.001) models. During recovery, the healthy control group had 5.9% decline in systolic BP per minute. In contrast, MUCH had only 3.3% per minute reduction and the UCH group had 0.3% reduction per minute. A test of linear trend was significant (P = 0.002, adjusted model). Conclusion Because there was no impairment in the heart rate recovery among groups, we speculate that the parasympathetic pathway appears intact among treated hypertensives with CKD. However, the failure to withdraw sympathetic tone upon termination of exercise causes ongoing vasoconstriction and delayed systolic BP recovery providing a biological basis for MUCH. Delayed recovery from exercise-induced hypertension in those with poorly controlled BP provides potentially a new target to assure round-the-clock BP control.Item Establishing the minimal sufficient number of measurements to validate a 24h blood pressure recording(2018-05-17) Agarwal, Rajiv; Tu, WanzhuBackground: Ambulatory blood pressure (BP) monitoring (ABPM) remains a reference standard but the number of readings required to make the measurement valid has not been empirically validated. Methods: Among 360 patients with chronic kidney disease and 38 healthy controls, BP was recorded 2 per hour during the night and 3 per hour during the day over 24h using a validated ABPM device; all had at least 90% of the expected readings. From this full set of ABPM recording, a variable number of BP measurements were selected and we compared the performance of the selected readings against that of the full sample using random or sequential selection schemes. To address the question whether random or sequential selection schemes affect the diagnostic performance in diagnosing hypertension control we compared the diagnostic decisions reached with the subsample and the full sample using area under the receiver operating-characteristic curves (AUC ROC). To answer the question regarding the number of readings needed to achieve over 90% coverage of the mean BP of the full ABPM sample we ascertained the point and confidence interval (CI) estimates based on the selected data. Results: To diagnose hypertension control, the number of readings randomly drawn to establish lower bound with 2.5% error of area under the receiver operating-characteristic curve (AUC ROC) of 0.9 was 3, 0.95 was 7, and 0.975 was 13 . In contrast, the corresponding number of readings with serial selections was 18, 30 and 39 respectively. With a random selection scheme, 18 readings provided 80% coverage of the 90th percentile of CI of the true systolic BP mean, for 90% coverage, 26 readings were needed, for 95% coverage 33. With serial selections, the number of readings increased to 42, 47, and 50 respectively. Similar results emerged for diastolic BP. Conclusions: For diagnosing hypertension control 3 random measurements or 18 serial measurements is sufficient. For quantitative analysis, the minimal sufficient number of 24h ambulatory BP is 26 random recordings or 42 serial recordings.Item Implications of Blood Pressure Measurement Technique for Implementation of Systolic Blood Pressure Intervention Trial (SPRINT)(Highwire Press, 2017-02-03) Agarwal, Rajiv; Medicine, School of MedicineBackground Cardiovascular morbidity and mortality was reduced by 25% when blood pressure (BP) was targeted to 120 mm Hg systolic compared with 140 mm Hg systolic in Systolic Blood Pressure Intervention Trial (SPRINT); however, BP was measured using a research technique. SPRINT specified 5 minutes of seated rest in a quiet room followed by 3 oscillometric measurements without an observer in the room. The relationship of this research‐grade methodology to routine BP measurements is not known. Methods and Results Among 275 people with chronic kidney disease who had BP <140/90 mm Hg when they came to the clinic, we measured BP as in SPRINT and recorded BP on the same day without specification of seated rest. Compared with routine measurement, the research‐grade systolic BP was 12.7 mm Hg lower with wide limits of agreement (−46.1 to 20.7 mm Hg). Research grade systolic BP was 7.9 mm Hg lower than daytime ambulatory systolic BP and had wide agreement limits (−33.2 to 17.4 mm Hg). Whereas the routine, research‐grade, and daytime ambulatory systolic BP were all related to echocardiographic left ventricular hypertrophy, the strength of the relationship between research‐grade and daytime ambulatory systolic BP to left ventricular hypertrophy was similar and stronger than the strength of the relationship between routine systolic BP and left ventricular hypertrophy. Conclusions Taken together, these results suggest that translation of the SPRINT results will require measurement of BP as performed in that trial. Instead of an algebraic manipulation of routine clinic measurements, the SPRINT methodology of BP measurement would be needed at minimum if implementation of the SPRINT results were to be deployed in the population at large.Item Minimally sufficient numbers of measurements for validation of 24-hour blood pressure monitoring in chronic kidney disease(Elsevier, 2018-12) Agarwal, Rajiv; Tu, Wanzhu; Medicine, School of MedicineAmbulatory blood pressure monitoring (ABPM) remains a reference standard, but the minimal number of ABPM readings required to diagnose hypertension has not been empirically validated. Among 360 patients with chronic kidney disease and 38 healthy controls, 24-hour blood pressure was recorded 2 times per hour during the night and 3 times per hour during the day. All subjects had at least 90% of the expected readings recorded. From this full set of ABPM recordings, we selected variable numbers of measurements and compared the performance of the selected readings against that of the full sample under either random or sequential sampling schemes. With 8 randomly selected systolic blood pressure readings, we were able to make diagnostic decisions in concordance with that from the full ABPM sample 91.0% of the time (kappa 0.804). With 15 randomly selected diastolic blood pressure readings, we made concordant decisions 96.3% of the time (kappa 0.810). A serial selection scheme generally required a greater number of readings to achieve the same levels of concordance with the full ABPM data. With a random selection scheme, 26 readings provided 95% confidence that the sample mean will be within 5 mm Hg of the true systolic blood pressure mean, and within 3.5 mm Hg of the true diastolic blood pressure mean.